Existing methods for diagnosing diseases, particularly diabetes, are often less than desirable. One such method, the oral glucose tolerance test, attempts to assist diagnosis of diabetes mellitus by determining whether elevated blood glucose levels exist in patients suspected of having the disease. Because many patients having elevated levels fail subsequently to develop the clinical symptoms of the disease, however, the reliability of the test is generally questioned.
A second diagnostic method, the Islet Cell Antibody (ICA) test, may be used to predict those patients at risk for type I diabetes and can predate the onset of debilitating clinical symptoms by as much as five years. The ICA test is not typically utilized, however, because of its complexity, expense, and lack of specificity and because of a lack of standardization among evaluating laboratories. Furthermore, the test is useful only for detecting type I diabetes, which strikes only approximately ten percent of the entire diabetic patient population. By contrast, patients suspected of having the prediabetic condition for type II diabetes currently have no confirming diagnostic procedure.
It is well known that certain portions of the eye fluoresce when illuminated. The lens of the eye, for example, can be made to fluoresce intensely when illuminated with radiation having a wavelength between approximately 350 nm and 550 nm. Utilizing radiation of a wavelength less than approximately 400 nm typically is avoided (unless power levels and exposure times are restricted), however, since this higher frequency radiation is known to cause damage to ocular tissue.
The presence of certain diseases in the human body cause chemical changes in the lens of the eye, altering the amount of the fluorescent response to an illumination of the lens. The lenses of cataract patients, for example, become opaque due to lipid peroxidation, protein glycosylation, and the conversion of sulfhydryl (--SH) bonds to disulfide bonds (--SS). Similarly, in diabetes mellitus and galactosemia, the glucose and galactose are converted to sorbitol and dulcitol, respectively. Accumulation of these compounds results in a high osmotic gradient within the lenticular cells. Prolonged therapy with drugs such as corticosteroids and chlorpromazine also causes opacities of the human lens.
U.S. Pat. Nos. 4,895,159 and 4,883,351 to Weiss (which patents are incorporated herein in their entireties by this reference), thus, disclose methods for detecting the existence of diabetes using light scattered from lenticular cells. As described in the Weiss patents, the backscattered light from a patient suspected of having diabetes is used to calculate a diffusion coefficient for that patient. A second determination of diffusion coefficients is made for a control group of nondiabetic patients, and the diffusion coefficient of the suspected diabetic is compared with those of nondiabetic, control group patients of the same age.
Because lenses typically cloud naturally as patients age, however, measurements made in connection with the methods of the Weiss patents can be taken only from clear sites in the patients' lenses. The Weiss techniques also appear unable to distinguish the ultimate cause of changes in diffusion coefficients or to detect the prediabetic condition (i.e. where no overt clinical signs of diabetes are displayed but will be exhibited within approximately five years as, for example, when a positive ICA test occurs), since myriad diseases and physiological conditions are known to affect the lens in the manner therein described. Use of the diffusion coefficient as a stand-alone diagnostic test also suffers from its variability as a function of patient age, particularly since results have both age-dependent and age-independent variance.
Other patents, such as West German Patent No. 261957A1 to Schiller and U.S. Pat. No. 4,852,987 to Lohmann (each of which is incorporated herein in its entirety by this reference), describe alternate diagnostic methods in which the fluorescence signal intensities are compared. The Schiller patent, for example, discloses comparing fluorescence signal intensities at two wavelengths using a single excitation wavelength in an effort to detect the presence of cataracts. The ratio of the resulting fluorescence intensities is compared to the ratio obtained at the same wavelengths from known cataract patients to achieve the desired diagnostic result. As described in the Schiller patent, the excitation wavelengths are selected from the ranges 320-340 nm, 380-390 nm, and 430-450 nm, while the intensity of fluorescence peaks is measured within wavelength ranges of 410-440 nm, 450-460 nm, and 500-520 nm. In contrast to the Schiller patent, the Lohmann patent measures the magnitude of fluorescence intensity at a single wavelength created by light of one excitation wavelength and compares this intensity to known intensities at the given wavelengths in order to determine the degree of eye lens cloudiness. Neither of these patents, however, teaches or suggests detection of diabetes or the prediabetic condition.